Acetylcholinesterase Inhibitors: Beneficial Effects on Comorbidities in Patients With Alzheimer’s Disease

Kaushik, Vinod; Smith, Sarah Toombs; Mikobi, Emmanuel; Raji, Mukaila

doi:10.1177/1533317517734352

Cited by 29 publications

(20 citation statements)

References 113 publications

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“…Meanwhile, we provided the first evidence that xanthoceraside treatment attenuated the deficits of social activities in the social interaction test. Donepezil, one of the acetylcholinesterase inhibitors, is used for the treatment of AD patients [43] and usually used as a positive drug for basic research [44]. Xanthoceraside (0.32 mg/kg) had better results in behavioral tests than donepezil (1.3 mg/kg).…”

Section: Discussionmentioning

confidence: 99%

Xanthoceraside prevented synaptic loss and reversed learning-memory deficits in APP/PS1 transgenic mice

et al. 2019

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Xanthoceraside, a novel triterpenoid saponin, has been found to attenuate learning and memory impairments in AD animal models. However, whether xanthoceraside has a positive effect on synaptic morphology remains unclear. Herein, we evaluated the effects of xanthoceraside on learning and memory impairments and the abnormalities of synaptic structure in APP/PS1 transgenic mice. The behavioral experiments demonstrated that xanthoceraside attenuated the imaginal memory and spatial learning impairments, and improved social interaction. Transmission electron microscopy and Golgi staining showed that xanthoceraside ameliorated synapse morphology abnormalities and dendritic spine density deficits, respectively. Western-blot analysis identified that xanthoceraside increased the expression of SYP and PSD95, activated BDNF/TrkB/MAPK/ERK and PI3K/Akt signaling pathways, meanwhile decreased the expression of RhoA, ROCK and Snk, increased the levels of SPAR, and activated the BDNF/TrkB/cofilin signaling pathway. Taken together, our study indicated that xanthoceraside improved cognitive function and protected both synaptic morphology and dendritic spine in APP/PS1 transgenic mice, which might be related in part to its activation in the BDNF/TrkB pathway.

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Section: Discussionmentioning

confidence: 99%

Xanthoceraside prevented synaptic loss and reversed learning-memory deficits in APP/PS1 transgenic mice

et al. 2019

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“…Because overexcited sympathetic function plays an important role in ischemic heart disease, the vagotonic stimulation of administrated acetylcholinesterase inhibitors might also provide beneficial effects [ 22 ]. Actually, recent studies provided strong evidences that donepezil reduces the risk of myocardial infarction and pacemaker implantation in subjects with AD [ 11 , 11 , 12 ].…”

Section: Discussionmentioning

confidence: 99%

Electrocardiogram Changes of Donepezil Administration in Elderly Patients with Ischemic Heart Disease

Wang

An-cai

et al. 2018

Cardiology Research and Practice

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Objective Donepezil, a widely used cholinesterase inhibitor for treating Alzheimer's disease, has been reported to induce bradyarrhythmias and torsade de pointes. In this study, we aimed at determining electrocardiogram changes of donepezil administration in elderly patients with ischemic heart disease, who tend to suffer from cognitive disorders. Methods Sixty patients with ischemic heart disease and mild cognitive impairment were treated with donepezil (5 mg/day) and followed up for at least four weeks. A twenty-four-hour ambulatory electrocardiogram was performed for the analysis of heart rate variability. The ECG parameters including heart rate (HR), PR and RR intervals, QT interval, and QRS duration were recorded at the baseline and after donepezil administration. Results Donepezil administration resulted in significant reduction in mean HR and the lowest HR and prolongation of PR and RR intervals, whereas it had no significant effects on QRS duration and QT parameters including QT, corrected QT interval, QT dispersion, and Tpeak-end interval. HRV analysis showed that donepezil administration significantly improved parasympathetic function, indicated by decreased low/high frequency (LF/HF) ratio and high frequency (HF) components and oscillation of RR intervals. Conclusions These data demonstrated that donepezil administration decreased HR, prolonged PR interval, and increased parasympathetic function without affecting QRS duration and QT intervals, suggesting that it can be used safely in elderly patients with ischemic heart disease.

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“…AD patients and animal models have obvious cholinergic dysfunction involving abnormal ACh production and degradation, including choline acetyltransferase (ChAT) and acetylcholinesterase (AChE), respectively (Davies and Maloney, 1976;Perry et al, 1977;Schliebs and Arendt, 2011). Acetylcholinesterase inhibitors (donepezil, rivastigmine, galantamine) are approved by the U.S. Food and Drug Administration for the treatment of AD patients (Unzeta et al, 2016;Kaushik et al, 2018;Alzheimer's Association, 2020). High levels of ACh contribute to hippocampal θ oscillation and enhance memory (Verdier and Dykes, 2001;Micheau and Marighetto, 2011).…”

Section: Regulation the Cholinergic Systemmentioning

confidence: 99%

Deep Brain Stimulation for Alzheimer's Disease: Stimulation Parameters and Potential Mechanisms of Action

Luo

Sun

Tian

et al. 2021

Front. Aging Neurosci.

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Deep brain stimulation (DBS) is a neurosurgical technique that regulates neuron activity by using internal pulse generators to electrodes in specific target areas of the brain. As a blind treatment, DBS is widely used in the field of mental and neurological diseases, although its mechanism of action is still unclear. In the past 10 years, DBS has shown a certain positive effect in animal models and patients with Alzheimer's disease (AD), but there are also different results that may be related to the stimulation parameters of DBS. Based on this, determining the optimal stimulation parameters for DBS in AD and understanding its mechanism of action are essential to promote the clinical application of DBS in AD. This review aims to explore the therapeutic effect of DBS in AD, and to analyze its stimulation parameters and potential mechanism of action. The keywords “Deep brain stimulation” and “Alzheimer's Disease” were used for systematic searches in the literature databases of Web of Science and PubMed (from 1900 to September 29, 2020). All human clinical studies and animal studies were reported in English, including individual case studies and long-term follow-up studies, were included. These studies described the therapeutic effects of DBS in AD. The results included 16 human clinical studies and 14 animal studies, of which 28 studies clearly demonstrated the positive effect of DBS in AD. We analyzed the current stimulation parameters of DBS in AD from stimulation target, stimulation frequency, stimulation start time, stimulation duration, unilateral/bilateral treatment and current intensity, etc., and we also discussed its potential mechanism of action from multiple aspects, including regulating related neural networks, promoting nerve oscillation, reducing β-amyloid and tau levels, reducing neuroinflammation, regulating the cholinergic system, inducing the synthesis of nerve growth factor.

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Acetylcholinesterase Inhibitors: Beneficial Effects on Comorbidities in Patients With Alzheimer’s Disease

Cited by 29 publications

References 113 publications

Xanthoceraside prevented synaptic loss and reversed learning-memory deficits in APP/PS1 transgenic mice

Xanthoceraside prevented synaptic loss and reversed learning-memory deficits in APP/PS1 transgenic mice

Electrocardiogram Changes of Donepezil Administration in Elderly Patients with Ischemic Heart Disease

Deep Brain Stimulation for Alzheimer's Disease: Stimulation Parameters and Potential Mechanisms of Action

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